Objective To investigate pharmacologically active components of Yiqi Zishen Formula(YZF)and their mechanisms for alleviating airway inflammation in mice with chronic obstructive pulmonary disease(COPD).Methods Ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry was employed to characterize the chemical components in YZF and YZF-medicated rat serum.A compound-disease target network was constructed based on serum components of YZF to screen the key pathways and targets using enrichment analysis.A mouse model of cigarette smoke-induced COPD was used to evaluate the anti-inflammatory effect of YZF and validate the expression of key proteins in network pharmacology-enriched pathways.Fifty male C57BL/6J mice were randomized equally into control group,COPD model group,high-and low-dose YZF treatment groups,and N-acetylcysteine treatment group.Pulmonary function of the mice was assessed using whole-body plethysmography,and lung histopathology,alveolar structure,and airway remodeling were analyzed using HE staining.The levels of IL-1β,IL-6,and TNF-α in bronchoalveolar lavage fluid(BALF)were determined with ELISA,and pulmonary expressions of PI3K,Akt,phosphorylated Akt(p-Akt),p65,and phosphorylated p65(p-p65)were detected using immunohistochemistry.Results We identified a total of 156 chemical components(including 26 flavonoids or flavonoid glycosides,27 alkaloids,and 11 saponins)in YZF and 43 prototype components in medicated rat serum.Network pharmacology revealed 704 YZF-related targets and 1199 COPD-associated targets.Integrated analysis suggested that the anti-COPD effects of YZF were associated with the PI3K-Akt signaling pathway.In mouse models of COPD,YZF treatment significantly increased mean alveolar number and peak expiratory flow(P<0.05),reduced mean linear intercept,bronchial wall thickness,lung coefficient,and BALF cytokine levels,and suppressed the expressions of PI3K,Akt,p-Akt,p65,and p-p65 in the lung tissues.Conclusion YZF alleviates COPD symptoms and airway inflammation in mice possibly by inhibiting the PI3K/Akt/NF-κB pathway through its multiple components that interact with multiple targets.

Neddylation is a crucial posttranslational modification that involves the attachment of neural precursor cell-expressed developmentally downregulated protein 8(NEDD8)to a lysine residue in the substrate via the sequential actions of the E1 NEDD8-activating enzyme(NAE)(E1),E2 NEDD8-conjugating enzyme(E2),and E3 NEDD8-ligase(E3).The most extensively studied substrates of neddylation are members of the cullin family,which act as scaffold components for cullin ring E3 ubiquitin ligases(CRLs).Since cullin neddylation activates CRLs,which are frequently overactive in tumors,inhibiting neddylation has emerged as a promising strategy for developing novel antitumor therapies.This review explores the antitumor effects of inhibiting neddylation that leads to the inactivation of CRLs and provides a summary of known inhibitors that target protein-protein interactions(PPIs)within the neddylation enzymatic cascade.

ObjectiveTo study the regulatory effects of Yinchenhao Tang combined with Yinchen Zhufu Tang on the expression of regulatory T （Treg）/helper T 17 （Th17） cells cultured in vitro from the patients with hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF）. MethodsFresh peripheral blood was collected from the patients with HBV-ACLF for the separation of peripheral blood mononuclear cells （PBMCs）. Immunomagnetic beads were used to isolate primary Treg and naive CD4⁺ T cells. After in vitro expansion， naive CD4⁺ T cells were induced to differentiate into Th17 cells. Rats were treated with the clearing method （Yinchenhao Tang）， warming method （Yinchen Zhufu Tang）， and combination of clearing method with warming method （Yinchenhao Tang combined with Yinchen Zhufu Tang， also known as Wenyang Jiedu Huayu Prescription）， respectively， and then the medicated plasma samples were collected. Meanwhile， blank plasma was collected from the rats treated with normal saline. Cells were classified into blank， clearing method （5.04 g·kg^-1）， warming method （6.21 g·kg^-1）， and combination of clearing method with warming method （17.1 g·kg^-1） groups and treated with corresponding plasma. The frequency of Treg/Th17 cells was detected by flow cytometry. The level of transforming growth factor-β （TGF-β） was measured by the enzyme-linked immunosorbent assay. The cytometric bead array （CBA） was employed to measure the levels of interleukin-10 （IL-10）， interleukin-17A （IL-17A）， tumor necrosis factor-α （TNF-α）， and interleukin-23 （IL-23）. The mRNA and protein levels of Forkhead box P3 （FoxP3） and retinoic acid-related orphan receptor-gamma t （ROR-γt） were determined by Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the combination of clearing method with warming method group showed decreased frequency of Treg and Th17 cells， lowered levels of Treg cytokines （TGF-β and IL-10） and Th17 cytokines （TNF-α， IL-17A， and IL-23）， and down-regulated mRNA and protein levels of FoxP3 and ROR-γt （P<0.01）. Compared with the clearing method group， the combination of clearing method with warming method group showed decreased Treg cell frequency and down-regulated mRNA and protein levels of FoxP3. Meanwhile， the combination group showed decreased Th17 cell frequency， lowered levels of TGF-β， IL-10， TNF-α， IL-17A， and IL-23， and down-regulated mRNA and protein levels of ROR-γt （P<0.05， P<0.01）. Compared with the warming method group， the combination of clearing method with warming method group showed decreased frequency of Treg cells and down-regulated mRNA and protein levels of FoxP3. Meanwhile， the combination group showed decreased Th17 cell frequency， declined levels of TGF-β， IL-10， TNF-α， IL-17A， and IL-23， and down-regulated mRNA and protein levels of ROR-γt （P<0.05）. ConclusionThe combination of clearing method with warming method can down-regulate the expression of specific cytokines of Treg and Th17 cells， inhibit the over activation of Treg and Th17 cells， and reduce the secretion of cytokines such as TGF-β， IL-10， TNF-α， IL-17A， and IL-23， thereby alleviating inflammation and improving the prognosis of the patients with liver failure.

ObjectiveTo investigate the differential expression of intestinal flora in patients with different traditional Chinese medicine （TCM） syndrome types （Yang Huang syndrome， Yin-Yang Huang syndrome， and Yin Huang syndrome） of hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF） and clarify the biological basis of jaundice and Yin Huang syndrome in liver failure. MethodsA total of 20 cases of HBV-ACLF patients were included in the Yang Huang group， 20 cases in the Yin-Yang Huang group， 16 cases in the Yin Huang group， and 20 healthy adult volunteers. 16S rRNA gene sequencing was used to detect the diversity， species distribution， and differences of the subjects' intestinal flora， and bioinformatics analysis was conducted. ResultsCompared with those in the healthy control group， the species richness and diversity of intestinal flora in the HBV-ACLF Yang Huang group， Yin-Yang Huang group， and Yin Huang group were significantly reduced， and there were significant differences in the composition of intestinal flora compared with healthy volunteers. However， there were no significant differences in the species richness， diversity， and composition of intestinal flora among the three groups. LEfSe analysis showed that compared with the healthy control group， the HBV-ACLF Yang Huang group showed significant enrichment of Staphylococcus aureus（P<0.01）. Yin-Yang Huang group showed significant enrichment of s_Ileibacterium valens（P<0.05，P<0.01）， and the Yin Huang group showed significant enrichment of Enterococcus faecium and Streptococcus sali varius（P<0.05）. These strains may be biomarkers between the three groups of patients and the healthy control group. Compared with that in the Yin-Yang Huang group， Tyzzerella_nexilis was significantly enriched in the Yang-Huang group， and Streptococcus lactiae was significantly enriched in the Yin-Yang Huang group. Compared with that in the Yang-Huang group and the Yin-Yang Huang group， Enterococcus faecalis was significantly enriched in the Yin Huang group. The above strains may be biomarkers among the three groups of patients， and Enterococcus faecium may be a biomarker for the transition from the Yang Huang group to the Yin Huang group. ConclusionsThere are significant differences in the intestinal flora between patients with HBV-ACLF Yang Huang syndrome， Yin-Yang Huang syndrome， and Yin Huang syndrome. Enterococcus faecium is significantly enriched in the Yin Huang syndrome group， suggesting that dysbiosis of the intestinal flora may be the biological basis for jaundice and Yin Huang syndrome in liver failure.

ObjectiveTo study the expression differences of regulatory T cells （Treg） and T helper 17 cells （Th17） in the peripheral blood of patients with hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF） in five types of traditional Chinese medicine （TCM） syndrome. MethodsA total of 144 patients with HBV-ACLF were included and divided into five types of TCM syndrome， including 34 cases of heat-toxin amassment syndrome， 44 cases of dampness-heat amassment syndrome， 27 cases of Qi-deficiency and stasis jaundice syndrome， 21 cases of spleen-kidney Yang deficiency syndrome， and 18 cases of liver-kidney Yin deficiency syndrome. Meanwhile， 30 healthy volunteers were included as controls. The frequency of Treg and Th17 cells in the peripheral blood of subjects in each group was detected by flow cytometry， and the Treg/Th17 ratio was calculated. Cytometric bead array （CBA） was used to detect the levels of cytokines interleukin （IL）-10， transforming growth factor-β （TGF-β）， tumor necrosis factor-α （TNF-α）， IL-17A， and IL-23. Real-time fluorescence quantitative PCR （Real-time PCR） detected the mRNA expression of forkhead box P3 （FoxP3） and retinoic acid-related orphan receptor gamma t （ROR-γt）. Results（1） Compared with that in the healthy control group， the frequency of Treg and Th17 cells in patients with various TCM syndrome types of HBV-ACLF increased （P<0.05）. Compared with that in the heat-toxin amassment syndrome group， the frequency of Treg and Th17 cells decreased in the dampness-heat amassment syndrome group （P<0.05）， while the frequency of Treg and Th17 cells increased in the Qi-deficiency and stasis jaundice syndrome group， spleen-kidney Yang deficiency syndrome group， and liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with that in the dampness-heat amassment syndrome group， the frequency of Treg and Th17 cells increased in the dampness-heat amassment syndrome group， spleen-kidney Yang deficiency syndrome group， and liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with that in the Qi-deficiency and stasis jaundice syndrome group， the frequency of Treg and Th17 cells increased in the spleen-kidney Yang deficiency syndrome group （P<0.05）， while the frequency of Treg and Th17 cells decreased in the liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with the spleen-kidney Yang deficiency syndrome group， the frequency of Treg and Th17 cells decreased in the liver-kidney Yin deficiency syndrome group （P<0.05）. （2） Compared with that in the healthy control group， the Treg/Th17 cell ratio in patients with various TCM syndromes of HBV-ACLF decreased （P<0.05）. Compared with that in the heat-toxin amassment syndrome group， the Treg/Th17 cell ratio increased in the dampness-heat amassment syndrome group （P<0.05）， while it decreased in the Qi-deficiency and stasis jaundice syndrome group， spleen-kidney Yang deficiency syndrome group， and liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with that in the dampness-heat amassment syndrome group， the Treg/Th17 cell ratio decreased in the Qi-deficiency and stasis jaundice syndrome group， spleen-kidney Yang deficiency syndrome group， and liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with that in the Qi-deficiency and stasis jaundice syndrome group， the Treg/Th17 cell ratio increased in the spleen-kidney Yang deficiency syndrome group and liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with the spleen-kidney Yang deficiency syndrome group， the Treg/Th17 cell ratio in the liver-kidney Yin deficiency syndrome group increased （P<0.05）. （3） Compared with those in the healthy control group， the levels of Treg-related cytokines IL-10 and TGF-β， as well as Th17-related cytokines TNF-α， IL-17A， and IL-23， were elevated in patients with various TCM syndrome types of HBV-ACLF （P<0.05）. There was no significant difference in TNF-α levels among different TCM syndrome types. Compared with those in the heat-toxin amassment syndrome group， the levels of IL-10， TNF-β， IL-17A， and IL-23 in the dampness-heat amassment syndrome group， Qi-deficiency and stasis jaundice syndrome group， spleen-kidney Yang deficiency syndrome group， and liver-kidney Yin deficiency syndrome groups increased （P<0.05）. Compared with those in the dampness-heat amassment syndrome group， the levels of IL-10， TGF-β， IL-17A， and IL-23 increased in the Qi-deficiency and stasis jaundice syndrome group， spleen-kidney Yang deficiency syndrome group， and liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with those in the Qi-deficiency and stasis jaundice syndrome group， the levels of IL-10， TGF-β， IL-17A， and IL-23 in the spleen-kidney Yang deficiency syndrome group increased （P<0.05）， while those in the liver-kidney Yin deficiency syndrome group decreased （P<0.05）. Compared with those in the spleen-kidney Yang deficiency syndrome， the levels of IL-10， TGF-β， IL-17A， and IL-23 in the liver-kidney Yin deficiency syndrome group decreased （P<0.05）. （4） Compared with that in the healthy control group， the mRNA of Treg/Th17 cell specific transcription factors FoxP3 and ROR-γt were elevated in patients with various TCM syndrome types of HBV-ACLF （P<0.05）. Compared with that in the heat-toxin amassment syndrome group， the mRNA of FoxP3 and ROR-γt increased in the Qi-deficiency and stasis jaundice syndrome group， spleen-kidney Yang deficiency syndrome group， and liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with that in the dampness-heat amassment syndrome group， the mRNA of FoxP3 and ROR-γt increased in the Qi-deficiency and stasis jaundice syndrome group， spleen-kidney Yang deficiency syndrome group， and liver-kidney Yin deficiency syndrome （P<0.05）. Compared with that in the Qi-deficiency and stasis jaundice syndrome group， the mRNA of FoxP3 and ROR-γt in the spleen-kidney Yang deficiency syndrome group increased （P<0.05）， and it decreased in the liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with that in the spleen-kidney Yang deficiency syndrome group， the mRNA of FoxP3 and ROR-γt decreased in the liver-kidney Yin deficiency syndrome group （P<0.05）. ConclusionThe frequency and ratio of Treg/Th17 cells， as well as the expression of related cytokines and specific receptors in peripheral blood of patients with HBV-ACLF in five types of TCM syndromes are different， which has certain reference value for TCM syndrome differentiation and treatment of patients with HBV-ACLF.

Lung cancer is one of the most lethal tumors in the world with a 5-year overall survival rate of less than 20%, mainly including lung adenocarcinoma (LUAD). Tumor microenvironment (TME) has become a new research focus in the treatment of lung cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. The various cellular components exert a different role in apoptosis, metastasis, or proliferation of lung cancer cells through different pathways, thus contributing to the treatment of adenocarcinoma and potentially facilitating novel therapeutic methods. This review summarizes the research progress on different cellular components with cell-cell interactions in the TME of LUAD, along with their corresponding drug candidates, suggesting that targeting cellular components in the TME of LUAD holds great promise for future theraputic development.
Humans ; Tumor Microenvironment/drug effects* ; Adenocarcinoma of Lung/drug therapy* ; Lung Neoplasms/pathology* ; Adenocarcinoma/metabolism* ; Animals ; Apoptosis/physiology*

Cancer represents a major worldwide disease burden marked by escalating incidence and mortality. While therapeutic advances persist, developing safer and precisely targeted modalities remains imperative. Nanomedicines emerges as a transformative paradigm leveraging distinctive physicochemical properties to achieve tumor-specific drug delivery, controlled release, and tumor microenvironment modulation. By synergizing passive enhanced permeation and retention effect-driven accumulation and active ligand-mediated targeting, nanoplatforms enhance pharmacokinetics, promote tumor microenvironment enrichment, and improve cellular internalization while mitigating systemic toxicity. Despite revolutionizing cancer therapy through enhanced treatment efficacy and reduced adverse effects, translational challenges persist in manufacturing scalability, longterm biosafety, and cost-efficiency. This review systematically analyzes cutting-edge nanoplatforms, including polymeric, lipidic, biomimetic, albumin-based, peptide engineered, DNA origami, and inorganic nanocarriers, while evaluating their strategic advantages and technical limitations across three therapeutic domains: immunotherapy, chemotherapy, and radiotherapy. By assessing structure-function correlations and clinical translation barriers, this work establishes mechanistic and translational references to advance oncological nanomedicine development.
Humans ; Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Nanoparticles/chemistry* ; Animals ; Nanomedicine/methods* ; Drug Delivery Systems/methods* ; Drug Carriers/chemistry* ; Radiotherapy/methods*

Objective:To investigate the denoising performance of different deep learning (DL) strategies on low-dose brain 18F-FDG PET images. Methods:This retrospective methodological study was conducted on brain PET/CT images of 50 patients (35 males, 15 females, age 20-87 years) who received 3.7MBq/kg 18F-FDG at the Fifth Affiliated Hospital of Sun Yat-sen University between May 2023 and January 2024. Full-dose PET data were acquired with 2min scan. CT scans were acquired before PET scanning. Low-dose PET sinograms were generated by down-sampling the full-dose list mode data to 1/2, 1/4, and 1/20 of full-dose count level. Both full-dose and low-dose sinograms were reconstructed with random, CT-based attenuation and scatter corrections using the three-dimensional (3D) ordered-subsets expectation maximization (OSEM) algorithm (2 iterations, 20 subsets). A total of 4 DL denoising methods were established: (1) 3D conditional generative adversarial networks (GAN) using only low-dose PET as input (GAN-1); (2) 3D attention-based GAN (AttGAN) with low-dose PET input (AttGAN-1); (3) 3D AttGAN with low-dose PET and CT inputs (AttGAN-2); (4) 3D AttGAN with frequency-separation using low-dose PET and CT inputs (AttGAN-FS-2). For AttGAN-FS-2, during the frequency division process, high- and low-frequency components were extracted from the PET reconstructed images via Fourier transform, then inversed Fourier transform, denoised separately, and finally combined to produce the final denoised images. The dataset was separated into training (70%), validation (10%) and testing (20%) sets using simple random sampling without replacement with a fixed random seed. A 5-fold cross-validation scheme was then applied to test all 50 patients. Performance was evaluated against full-dose PET using normalized mean square error (NMSE), structural similarity (SSIM), peak signal-to-noise ratio (PSNR), contrast-to-noise ratio (CNR), SUV mean and SUV max bias of selected brain ROIs. Wilcoxon signed rank test was used to analyze the differences between the denoising methods. Results:AttGAN-FS-2 showed the best performance among all dose levels, with statistical difference as compared by low-dose PET and GAN-1 denoised images for NMSE, SSIM, PSNR, and CNR ( Z values: 2.92-6.15, all P<0.005). NMSE, SSIM quantitative evaluation results (median) of each model at 1/20 dose were: GAN-1: 0.08, 0.87, AttGAN-1: 0.08, 0.88, AttGAN-2: 0.07, 0.89, AttGAN-FS-2: 0.06, 0.91, respectively ( Z values: 3.24-5.77, all P<0.005). Conclusion:The DL-based method combined with multiple strategies AttGAN-FS-2 shows improved denoising performance for low-dose brain PET images.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.